Abstract

Transition metal‐catalyzed hydrofunctionalization of alkynes and, more precisely, the intramolecular hydro‐oxycarbonylation (cycloisomerization) of acetylenic acids, has been widely employed as a key step in cascade processes for the construction of valuable and complex molecules. However, in contrast with other aminonucleophiles, no method has been reported for the reaction between primary monoamines and non‐activated alkynoic acids. Hence, a procedure has been devised for the regio‐ and diastereoselective preparation of 5‐alkylidene‐γ‐lactams via a copper‐catalyzed cascade reaction between alkynoic acids and amines. The developed protocol proves to be scalable and demonstrates significant tolerance to a wide range of structurally diverse alkynoic acids and amines bearing various functional groups, as evidenced by 60 high‐yielding examples. An exhaustive experimental and computational analysis of the reaction is also provided to unravel the nature and role of the copper catalyst, the observed regioselectivity and the mechanism of the reaction.